A new program to maintain readiness to investigate in the laboratory any newly recognized emerging infectious disease caused by a virus is being developed. Research on SEN-V Virus: SEN-V virus is a recently described DNA virus that is frequently detected in non-A to -E post-transfusion hepatitis. Two variants of the virus (subtypes C/H and D) have been reported to be hepatitis-related and have been reported in approximately 2% of U.S. volunteer blood donors. We evaluated the prevalence of these two variants of the virus in patients with hepatocellular carcinoma (HCC). A serum panel was constructed from 50 patients with HCCs (31 from Canada [eight with Asian surnames] and 19 from Japan). Coded duplicate samples and negative controls were included in the panel. Each sample was tested for the hepatitis B surface antigen (HBsAg), antibody to the hepatitis B core antigen (anti-HBc), and antibody to the hepatitis C virus (anti-HCV) by EIA. Fragments of SEN-V subtypes C/H and D were amplified by single-step PCR and analyzed by a DNA-enzyme immunoassay method. Eighteen of the 50 HCC patients (36%) were found to have SEN-V DNA of either subtype C/H or D in their serum (10/31 [32%] Canadian patients; 8/19 [42%] Japanese patients). SEN-V DNA was detected in 10/23 [43%] HCC patients with anti-HCV, 6/11 (55%) with HBsAg, and 1/7 (14%) without anti-HCV or HBsAg. HBsAg seronegative-HBV infections, characterized by the detection of HBV DNA in liver tissue or HCC in the absence of detectable HBsAg in serum, were documented in nine patients, or whom one (11%) had SEN-V in serum. Reproducibility of the SEN-V assay was confirmed by the detection of identical results in all duplicates except one. All six negative controls were negative for SEN-V DNA. SEN- V DNA was detected in serum in 32% of HCC patients from Canada and 42% of HCC patients from Japan and was typically found with coexistent HBV or HCV infection. SEN-V was found in only a small minority of patients with HCC unrelated to HBV or HCV and does not appear to be an important independent cause of cryptogenic HCC. This study could not ascertain whether SEN-V played a contributory role in carcinogenesis with HBV and HCV infections.